SOCS-1 deficiency does not prevent diet-induced insulin resistance.
Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling. Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance. Using SOCS-1 knockout mice, we investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD). SOCS-1 knockout mice on HFD gained 70% more weight, displayed a 2.3-fold increase in epididymal fat pads mass and increased hepatic lipid content. This was accompanied by increased mRNA expression of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver. HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests. Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.
Emanuelli
Brice
B
Hormone and Obesity Research, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Macotela
Yazmin
Y
Hormone and Obesity Research, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Boucher
Jérémie
J
Hormone and Obesity Research, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Ronald Kahn
C
C
Hormone and Obesity Research, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: c.ronald.kahn@joslin.harvard.edu.
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000235:genetics*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D004041:Dietary Fats; C499308:Rag2 protein, mouse; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins